Due to negligence or errors, laboratory mice at UCSF had toes removed without anesthesia. Several animals, including birds and a squirrel monkey, received little or no pain medication after surgical procedures. In one instance, a primate starved for weeks. In another, mice died of thirst. And for nearly two years, a rhesus monkey remained in a brain study despite chronic and painful complications.

A Chronicle review of laboratory inspection reports by the U.S. Department of Agriculture's animal welfare division, and an examination of UCSF's internal list of incidents, reveal that in the seven years after UCSF paid more than $90,000 to settle federal findings that its researchers violated the Animal Welfare Act, incidents of animal neglect or mistreatment have persisted.

Some were violations of the federal law, which covers mammals larger than rodents. Other incidents involved the many other animals protected by research protocols that demand humane treatment of all creatures, from reptiles to rats.

UCSF has one of the largest medical research programs in the country and relies on hundreds of thousands of animals as its researchers try to develop treatments for diseases of all kinds. Last year, 85 percent of its lab animals - nearly 800,000 - were rodents, fish, amphibians and reptiles, the university said. UCSF also used 98 primates, 162 birds and 467 rabbits.

The USDA enforces the Animal Welfare Act at research institutions around the country, usually with one unannounced visit a year. The inspectors look for violations, which can trigger a second unannounced visit to see if they're fixed. Repeated violations can lead to fines.

Inspectors also issue citations if an institution fails to follow research protocols established by its own animal oversight committee. The panels are charged with minimizing lab animals' pain and suffering.

Oversight committees

Researchers are also required to report negligence or errors to their animal oversight committees, which at UCSF has led to experiments being canceled and employees being retrained or fired.

University officials declined to be interviewed on matters concerning animal welfare. Instead, they responded in writing to questions relayed through a spokeswoman.

"The university takes very seriously the care and use of the animals it studies, beginning with ensuring that as few animals as possible are used in research," spokeswoman Barbara French said in a statement.

She said UCSF uses computer models and cultured cells for research if it can. If those won't work, researchers turn to animals.

The university has had no federal penalties imposed since 2005. But inspectors have cited UCSF repeatedly since then for violating the Animal Welfare Act or for violating its own research protocols.

UCSF's size cited

Asked why problems persist, French said that "failures to follow policies, guidelines and protocol can occur" at large medical or research programs. Considering its size, UCSF has had few incidents, she said.

Some of the federal citations have involved dirty or contaminated conditions, such as machinery oil leaking into cages awaiting animals. Others were for causing unnecessary pain and distress to animals.

This year, for example, inspectors cited UCSF for poor monitoring of eight voles, a type of rodent, in a degenerative brain disease study.

Researchers were supposed to record signs of disease before euthanizing the animals "at the earliest point possible" to avoid unnecessary suffering. But an inspector found that no one monitored the infected voles over a weekend. Three died of brain disease without yielding any data for the study, and all may have suffered unnecessary "discomfort, distress and pain," federal inspectors said.

It was a repeat violation. That and other violations led federal inspectors to make a second, unannounced visit in June that produced no further citations.

David Sacks, a USDA spokesman, declined to compare UCSF's performance with that of other institutions, saying that even one violation can be more egregious than many less-serious ones. He called the Animal Welfare Act a baseline and said institutions "have to follow protocols to the letter."

"The goal is for these facilities to adhere to these regulations every day," Sacks said. "Then we know that those animals at a minimum are receiving humane care and treatment."

In 2005, UCSF was required to pay $92,500 to settle violations cited by the USDA from 2001 to 2003. Veterinarians weren't providing proper care for many animals, including primates, sheep, lambs and rabbits, inspectors found, and UCSF's animal oversight committee wasn't properly reviewing or approving research protocols.

The penalty was among the largest ever imposed for violations of the Animal Welfare Act.

"It's a very substantial monetary penalty," Sacks said. "In terms of our enforcement actions, we want them to match appropriately with the nature of the violations."

Not everyone agrees that the penalties are large enough to be a deterrent.

Lucrative grants

"You would think that UC would clean up its act and not have these deficiencies anymore. But $92,000 is chump change for them because these research grants bring in millions - it's the cost of doing business," said Lawrence Hansen, a neuropathologist at UC San Diego who sued UC in 2007, saying state money was being used to support animal cruelty. A Superior Court judge called it a federal issue and dismissed the case.

"I don't disapprove of the use of all animals in research, as long as the animals don't suffer," said Hansen. "What they're doing to these monkeys is so inherently cruel and painful that it's impossible to do it without causing a great deal of pain and suffering."

Concerned that the federal law is too weak to protect lab animals from unnecessary harm, animal rights groups try to monitor their welfare by combing through inspection reports.

Rhesus in pain

According to the report and UCSF's account, the female monkey that UCSF researchers named Petra arrived at the lab in March 2008. In December, researchers studying Parkinson's disease implanted a device in the monkey's skull so that gene therapy could be delivered directly to her brain.

The device remained in place for seven months and was removed in July 2009. As is common practice, said UCSF, the veterinarian left screws in the monkey's skull.

Soon the monkey became lethargic and picked continually at the spot on her head. The veterinary staff treated her with antibiotics and painkillers. That didn't work, so a month later veterinarians tried to repair the wound surgically. That didn't work either, and in September they removed the screws.

It still didn't help. Her wound still unhealed, the monkey remained in the study. A year later, in October 2010, the veterinarians and principal researcher tried again to figure out the cause of the monkey's persistent wound. This time they found a piece of acrylic that had been left in her head from the 2008 implant.

A federal inspector arrived unannounced days later and snapped a photo of a miserable-looking monkey, a wide, red wound at the top of her head. Researchers euthanized Petra three weeks later, on Nov. 16, 2010.

The inspector returned in January 2011 and reviewed the records.

"Allowing an animal to remain on a study for almost two years while undergoing repeated invasive treatments for chronic complications of the study is not consistent with the intent of this section of the Animal Welfare Act," the inspector wrote. "Keeping an animal on study under these circumstances does not avoid or minimize discomfort, distress, or pain to that animal."

The inspector also cited UCSF for failing to remove foreign material, a violation of the research protocol. Although the university says its study led to a clinical trial now under way, the inspector made it clear that Petra should not have been involved once her distress was evident.

PETA challenge

"There are many thousands of animals suffering every day, and on top of that, you have UCSF failing to provide many of them with adequate veterinary care when they're sick," said Justin Goodman of PETA, which is calling on the National Institutes of Health to require UCSF to return the $2.1 million grant that funded the study in which Petra was involved.

The National Institutes of Health require grant recipients to adhere to the NIH's own lab animal welfare policy, but won't discuss or confirm active cases.

Once concluded, however, all reports become part of the public record.

Overall, UCSF hasn't been cited for the kind of vast systemic violations that happened a decade ago. But many of the violations do echo that period, including failing to adequately observe animals after surgery, giving them too little water or food, and neglecting to keep their enclosures clean.